Electrical apparatus for fiber detection



Aug. 16, 1966 B. B. YOUNG 3,267,363

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3/?(5 a yaw/6 RfACT/O/V MIXTURE 4140/0 a J 2 M M United States Patent3,267,363 ELECTRICAL APPARATUS FOR FIBER DETECTION Bruce B. Young,Radnor, Pa., assignor to Becton,

Dickinson and Company, Rutherford, N.J., a corporation of New JerseyFiled Apr. 18, 1962, Ser. No. 188,485 5 Claims. (Cl. 324-30) Thisinvention relates to electrical conductivity detection apparatus and,more particularly, to a system for detecting the presence of aparticular resistive medium in liquids.

There are a number of applications in which it is desirable to detectthe presence of an electrical resistive body of rather minutedimensional proportions. For example, the presence of fibers or similarstructural members in liquid or the initiation of fibrillation therein,in many fields, may be a critical factor. The formation of fibers isextremely significant in blood coagulation. In this connection, theclotting capabilities of a patients blood, its characteristics andclotting times and the hemotosis mechanism in general have an importantbearing in surgery and therapy. With this in mind, the coagulationproperties of blood plasmas are ordinarily measured for such indiagnostic and therapy control. It has been proposed that suchmeasurements be made in terms of time. That is the time in which liquidblood transforms into a semi-solid gel-like state of consistency.

=In particular, the hemotosis mechanism is evaluated in many instancesby prothrombin time determinations. Prothrombin time is defined as theperiod required for a particular specimen of prothrombin to induce bloodplasma clotting under standardized conditions in com: parison withnormal human blood. With respect to the latter the time is usuallybetween 11.5 and 12 seconds. If there is a departure, either a faultytechnique or mechanism is involved.

Clotting is essentially a function of the plasma and involves thechanging of one of the plasma proteins, fibrinogen, from the sol(liquid) to the gel (solid) state. The change in consistency is broughtabout by tiny, threadlike insoluble structures in which form aninterlacing network of fibers, made of a protein called fibrin.

The clotting processes are initiated and accelerated by the juices frominjured tissues. Both injured tissues and disintegrating blood plateletsgive ofr" similar substances, collectively thrombokinase, which initiatethe clotting reaction. Clotting, thusly occurs automatically at theproper time. When blood escapes from an injured vessel it is immediatelyexposed to juices from damaged tissue and its platelets disintegratereleasing additional throm'bokinase.

Thrombin is the immediate factor in the mechanism which changesfibrinogen into fibrin and produces the clot. Thrombin exists in theblood in an inactive form, prothrombin, which is changed bythrombokinase and calcium into thrombin at the time of clotting.Prothrombin itself does not occur as such in normal plasma, but iscombined with a substance called anti-prothrombin, with 'whichthrombokinase is united in order to initiate the clotting mechanisms.This union releases the prothrombin. This prothrombin is changed intothrombin by the presence of calcium. The thrombin together withfibrinogen, the soluble protein present in normal plasma, producefibrin, the insoluble protein which constitute the actual clot.

In accordance with a particular proposed technique for medical as wellas clinical use, standardized and stabil-ized chemical reagents areplaced in tubes and heated to normal body temperatures, notably 37 C.the accepted ions.

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standard. Ordinarily, a reagent will include various activators forcausing plasma to experience thrombosis. Such activators may includethromboplastin and calcium Reagents of this type are availablecommercially as for example, Calsoplastin, a reagent composedessentially of thromboplastin extract with calcium chloride added. Thequantity of reagents is ordinarily fixed for proper prothrombin timedeterminations. With this in mind, controlled plasma at the standardoperating temperature and of the predtermined quantity also in tubes, isthen dispensed in one of the tubes containing reagent. A probe is theninserted and withdrawn from the reaction mixture for purposes of sensingthe initial clot formation. This operation is also conducted at thestandard operating temperature. The same procedure is foil-owedutilizing a controlled amount of patien-ts plasma. The prothrombin timesare read and recorded.

Quite obviously, unless this procedure is controlled and accuratelyconducted inaccurate and erroneous results are inevitable. Under suchcircumstances, this may reflect in improper therapy administration.Unless, conducted efiiciently and expeditiously in case .of emergencies,errors will be compounded and multiplied.

It is therefore, a principle object of this invention to eliminate thedrawbacks and disadvantages mentioned in the above and at the same timeprovide for accurate, automatic means for sensing and detecting thepresence of a particlular resistive medium in liquids.

Another object is to provide for such sensing means, together withpositive indication and recordation of the time factor for completingthis determination.

A further object is to provide highly sensistive, electrical circuitryfor detecting the initiation of fiber formation incident tofibrillation.

An important object is to provide for the above in prothrombin andcoagulation time determinations and in measurements of the coagulationproperties of blood and blood plasma. i

Although the present invention has wider application in measuring theproperties of liquids or the detection of particular materials therein,the disclosure will be devoted primarly to prothrombin timedeterminations. It should be understood, however, that the invention isnot to be construed as being limited thereby because of the contemplatedbroad applications.

With this in mind, the present invention briefly stated includes aDarlington coupling of transistors having their respective collectorstied directly to one another. This coupling has the effect of permittingthe transistors to perform substantially as if only a single transistorwere present but permits greater current gain. In this connection, thehigher current gain is advantageously utilized to drive a relay. At thesame time, however, this transistor coupling provides a smaller currentthrough detecting probes.

These probes are employed in detecting the presence of a particularmedium or the initiation of fibrillation in the selected liquid. One ofthe probes is movable, whereas the other is stationary. The movableprobe is inserted into and removed from the liquid in a timed sequence.The low current is only adapted to flow through the probes when themovable probe is elevated above the surface of the liquid. Under suchcircumstances, when a fiber or more than one adheres to this probe andat the-same time extends into the liquid, a circuit is completed. Whenthe resistance of the fiber is detected the transistors are placed in anon-conducting state so as to de-energize the relay, which, in turn,serves to stop the running of the timer. The time for fibrillation isthen recorded.

The movable probe is automatically operated and is driven by a motor. Acomplete cycle into and out of the liquid material traverses in the caseof prothrombin time determinations, approximately two cycles per second.The motor additionally serve to rotate a magnet which is adapted to passin close proximity to a magnetically excitable switch during eachrevolution. In this manner, an electrical pulse is generated whichenergizes a counter, thereby recording time. Thus pulsing is variableand in the above specific application may be every tenth of a second.The circuit for both the timer and probes is closed deliberately andautomatically opened upon detection of a resistive fiber of the liquid.

Other objects and advantages will become apparent from the followingdetailed description which should be taken in conjunction with theaccompanying drawing, illustrating a somewhat preferred embodiment ofthe invention and in which the sole figure is a diagrammatic view ofelectrical circuitry incorporating the teachings of the presentinvention shown in association with stationary andmovable probes in areaction mixture in a tube, all of which are supported by a frame shownfragmentarily.

In the figure a pair of probes and 12 are shown disposed above frame 16.Probe 10 is stationary and electrically grounded, whereas probe 12 ismovable. Frame 16 may conveniently mount the components of theelectrical circuitry of this invention and may include a heating blockhaving coupled thereto suitable heaters and thermostats for maintainingstandard operating temperatures as is preferably the case in bloodplasma prothrombin time determinations. The frame 16 may, additionally,include a reaction well 18 adapted to advantageously receive a tube 20for containing the reaction mixture or liquid to experiencefibrillation. The probe 12 is preferably movable in a substantiallyvertical path or sweep in order that it may be immersed in the liquid 22and then removed to complete a single cycle. In time, this probe 12 willeventually have one or more fibers clinging thereto when elevated and atthe same time suspended in the liquid 22 to complete an electricalcircuit between the probes.

The movable probe, as shown, rests on a stepped cam 24 which is adaptedto raise the movable probe 12 and then lower it into the liquid 22 twiceeach cam revolution. This cam '24 is fixed to the output shaft of motor26 which is a constant speed motor adapted to rotate its output shaft ata rate of one revolution per second. Motor 26 is a single unit thoughshown twice in the drawings. It should be understood, that the rate inwhich the movable probe is raised and lowered, the configuration of thecam 24 and the characteristics of the output of its motor 26,particularly, may be varied depending upon the liquid to be tested forfibrillation. Furthermore, although in this disclosure the specificembodiment is directed to the application of fibrillation detection.

Referring now to the remainder of the circuitry illustrated, leads 30and 32 extend to the selected electrical energy source and may includesuitably rated fuses. These leads are connected to the primary winding34 of stepdown transformer 36. The secondary winding 38 of thistransformer is coupled with resistors 40 and 42. A rectifying diode 44is connected with resistor 40 and then to chassis ground, as shown. Theresistor 42 is likewise connected with a diode 46 which, in turn, isconnected between the junction of diode 44 and ground and, at the sametime, with the center-tap of the transformer 38. Filtering capacitors 48and 50 are interposed at each side of this connection with the centertap. The center tap of the transformer 38 is then coupled with theemitter of the transistor 52 forming part of a Darlington coupling inwhich transistor 54 is included. The collectors of these transistors inthis coupling are tied directly to one another, as shown, whereas, thebase of transistor 52 is connected with the emitter of transistor 54.The base of transistor 54 is connected with the diode 46 throughinterposed resistor 56. The junction between this resistor 56 and diode46 is connected to one side of relay 58. The other side of this relay 58is connected to the junction of the transistor collectors through itsnormally opened switch 60.

It should be understood that the coupling of the transistors 52 and 54with their collectors tied directly to one another permits them toperform essentially as a single transistor but with greater currentgain. This higher current gain provides an adequate drive for the relay58 while, at the same time, provides for a smaller current through theprobes. By having a greater current to the relay,.it is possible to usea less sensitive and hence a less expensive relay.

A jack 62 is connected across the switch and may be employed to connectthe circuit to an externally located switch for manually or, for thatmatter, automatically energizing the circuit. In this manner, the relayswitch 60 may be bypassed.

The junction between resistor 56 and the base of transistor 54 iselectrically connected with the movable probe 12. A switch 64 may beinterposed between this connection. This switch 64 is actuated by theoperation of the output shaft of motor 26. Accordingly, the opening andclosing of the switch 64 will be synchronized with the vertical movementof the movable probe 12. This can be accomplished through the operationof cam 24 if desired. Thus, when concerned with fibrillationapplications, the circuit between the movable and stationary probes 12and 10 will be open when the movable probe 12 is lowered into the liquidor reaction mixture 22 but will close when the probe 12 is raised fromthe liquid 22. Under such circumstances, a circuit will be completedbetween Ithe probes only at such time as an electrical con- .ductive.fiber is lifted by the movable probe 12 from the liquid 22.

Referring now to the motor and timer circuit of this invention, it willbe observed that this circuit is connected across the leads 30 and 32and is adapted to be opened and closed by means of the switch 68. Thisswitch, as

well as switch 60, is adapted to be manually closed and then held in aclosed position by the energization of its relay 58. As will beexplained in detail shortly, when a fiber is detected by the movableprobe 12, the circuit to the relay 5-8 is shorted, thereby resulting inits de-energization. Consequently, the switches 60 and 68 will open. Themotor 26 is included in this circuit and is series connected with theswitch 68. Connected across the motor 26 and in series with the switch68 is a reed switch 70 which is adapted to close by means of the magnetrevolvable with the output shaft of the mot-or 26. For purposes of thepresent discussion, the magnet, through a suitable gear network willrevolve at a rate ten times faster than the motor output shaft therebyclosing the switch 70 every tenth of a second. This switch 70 isconnected to one side of a diode bridge rectifier 72, both of which areconnected across the motor 26. The signal rectified by the diode bridge72 serves to actuate the drive of a digital counter 74 which will recordeach pulse received incident to the closing of the reed switch 70. Suchdigital computers or digital counters are well known and commerciallyavailable.

In the operation of the present invention, the electrical leads 30 and32 are connected With the electrical energy source. The tube 20 is thenplaced in the reaction well 18 of the test unit 16 and is then providedwith the reaction mixture liquid 22 to be subjected to fibrillation,with one or more of the constituents being already contained in the tubeor dispensed therein to initiate the reaction. For example, the tube mayinitially contain the selected chemical reagent in measuring thecoagulation properties of blood plasma. A predetermined dosage of bloodplasma would then be inserted. The stationary probe !10 and movableprobe -12 are immersed in the mixture 12 at the inception of thereaction orafter a short time delay if desired. Immediately thereafter,switch contacts 60 and 68 are simultaneously closed; at this time, therelay 58 is energized to maintain its switches 60 and 68 in a closedcondition, thereby eliminating the need to manually maintain theseswitches in this position. The motor 26 will accordingly be actuated toimpart rotation to its output shaft, and, consequently, to the drivenmagnet coupled therewith for rotation. Upon each traversal of the magnet.past the reed switch 70, an electrical pulse will be rectified by thediode bridge 72 to actuate the counter 74. As stated, the pulsing of thecounter may be selected to occur at tenth of a second intervals.

The center tap of the transformer 38, as well as the junction betweencapacitor 50 and diode 46, will be at nominal negative 'D.C. voltageswith the voltage .at the center tap being ordinarily less than that atthe capacitor and diode junction. The motor 26, as stated, through theoperation of the cam 24 will raise and lower the movable probe 12 out ofand into the reaction mixture 22 at the selected and preset rate.

The cycle of movement of the movable probe 12 is predetermined and inthe case of prothrombin time determinations may be at the rate of twocycles per second. In this connection, when the movable probe isimmersed in the liquid 22 the switch contact 64 is opened so that thecurrent path between probes through the liquid will not have an effecton the circuit. When the movable probe is elevated or raised above theliquid level the switch contact 64 closes. However, in view of theextremely highly resistant airgap between movable probe 12 and liquid 22the transistors 52 and 54 -are in a conducting state. Whenever theresistance measured across switch 64 and the probes and '12 to groundexceeds the value of resistance 56, the voltage at the base oftransistor 54 is more negative than the voltage at the emitter oftransister 52. This is because of the voltage dividing action ofresistance 56 and the resistance across the probes I10 and 12, both ofwhich are in series between the higher negative voltage and ground.Under this condition, tr ansistors 52 and 54 are in the conducting stateand current flows from the transformer center tap through the emitterand collector of the transistor 52, through the relay contact switch 60,the relay coil 58 and back to junction of capacitor 50 and diode 46. Ifthe resistance across the probes 10 and 12 to ground becomes lower thanresistance 56, as for example, when a fiber is lifted by the movableprobe 12 from the liquid 22, the transistors 52 and 54 switch to thenonconducting state. In this connection, ground or a positive voltagewill be applied to the base of the transistor 54. This bias serves toturn off the transistors. The relay 58 will, as a consequence, becomede-energized opening its switch contacts 60 and 68 thereby stopping theoperation of the motor 26. The counter 74 and movable probe 12 willcease operating. Accordingly, the time period in which the fibrillationprocess is initiated will be recorded.

In one illustrative embodiment applicable to prothrombin timedeterminations the following values for the various components of thecircuit were found satisfactory.

Resistor:

42 47 S2. 56 510 K9 Capacitor:

48 50 mfd. 50 50 mfd. lDiode:

Diode bridge rectifier 72, each diode 1lN1693.

Transistor:

54 2N1373. Motor 26 Synchron motor, Hanson Mfg. Co. Switch 70 MagneticReed Switch, Hamlin. Counter 74 Veeder Root Counter, Veeder Root Mfg.Co.

Probes 10 and 12 Stainless Steel.

Transformer 3 6 With v. applied across the primary at 50 to 60 c.p.s.,designed to supply 32 v. at 10 ma. at two secondary end taps and afterfiltration by diodes 44 and 46, 50 ma. rD.C. current. The voltage at theemitter of transistor 52 was -20 v. and at the junction of resistor 56and diode 46 was ---40 v.

Aliquots of plasma were blown into thromboplastin reagent and theswitches 60 and 68 substantially simul taneously pressed to initiate themovement of the probe 12. The reaction well column was calibrated forapproximately 0.3 ml. with 0.2 ml. for reagent plus 0.1 ml. for plasma.The probe movement was such as to duplicate manual techniques in thatthe electrode movement was identical to that of trained techniciansusing a wire loop. Thus, the guesswork in determining end points in thetime determinations was eliminated. The moving electrode alternatelydescended and lifted to seek and sense initial clot formation. When theend point occurred, the moving electrode 12 and the timer stopped. Theprothrombin time in seconds and 0.1 seconds were registered on thedigital read out 74.

The stationary probe 10 and movable probe 12 were raised from thereaction well and placed in a rest position. The digital read out 74 wassuch that by merely depressing a reset button the counter was cleared.The electrodes 10 and 12 only required cleaning by wiping and wererepositioned at rest in readiness for subsequent tests.

Thus the aforementioned objects and advantages are most effectivelyattained. Although a single somewhat preferred embodiment of theinvention has been described and illustrated herein it should beunderstood that the invention is in no sense limited thereby and is tobe determined by the scope of the appended claims.

I claim:

1. An electrical circuit for detecting the presence of fibrin in a bloodspecimen in :prothrombin time determinations comprising: a pair ofelectrodes, one of said electrodes being movable into and out of saidspecimen and the other of said electrodes being stationary in saidspecimen, drive means for moving the movable electrode into and out ofsaid specimen, first switch means in said circuit for permitting anelectrical potential to be applied across said electrodes,synchronization means synchronized with the operation of said drivemeans for removing the electrical potential across said electrodes whensaid movable electrode is immersed in said specimen and for permittingthe application of said electrical potential when said movable electrodeis out of said specimen, said synchronization means including switchclosing means for closing said switch upon lifting of fibrin from saidspecimen by the movable electrode to thereby provide a current pathbetween said electrodes through the fibrin and specimen, and electricalmeans in response to said switch closing means for deactivating theoperation of the drive means when the current path between saidelectrodes is so provided, a second switch means for energizing saiddrive means, magnetic means driven by said drive means, a magneticallyexcitable switch adapted to be closed upon each traversal of saidmagnetic means in close proximity thereto, a counter coupled with saidmagnetically excitable switch and adapted to register a digital amountupon each closure of said magnetically excitable switch.

2. The invention in accordance with claim 1 wherein relay means arecoupled with said first switch means and adapted to be energized uponclosure of said first switch means and adapted to maintain said firstswitch means in a closed position, and means for de-energizing saidrelay means and consequently open said first switch means upon detectionof the presence of fibrin in the blood specimen between said electrodes,a power supply section including a transformer, a pair of diodes coupledwith the secondary of said transformer, surge limiting resistors inseries with each of said diodes, and filter capacitors connected withone end of each of said diodes and to one another.

3. The invention in accordance with claim 1 wherein relay means arecoupled with said first switch means and adapted to be energized uponclosure of said first switch means and adapted to maintain said firstswitch means in a closed position, and means for de-energizing saidrelay means and consequently open said first switch means upon detectionof the presence of fibrin in the blood specimen between said electrodes,and a pair of connected transistors in cascade having their collectorselectrically tied to one another for providing sufiicient current todrive said relay means.

4. The invention in accordance with claim 3 wherein one of saidelectrodes is movable, a resistance is coupled with the base of thesecond transistor in cascade, and said movable electrode is connectedwith the juncture of said resistance and the base of said secondtransistor, and when the current path between said electrodes is closed,said transistors switch to a non-conducting state thereby de-energizingsaid relay.

5. The invention in accordance with claim 1 wherein a diode bridgerectifier is in series with said magnetically excitable switch, and saiddiode bridge rectifier is coupled with said counter and adapted tosupply a direct current pulse thereto upon each closure of saidmagnetically excitable switch.

References Cited by the Examiner UNITED STATES PATENTS WALTER L.CARLSON, Primary Examiner.

FREDERICK M. STRADER, Examiner.

C. F. ROBERTS, Assistant Examiner.

1. AN ELECTRICAL CIRCUIT FOR DETECTING THE PRESENCE OF FIBRIN IN A BLOODSPECIMEN IN PROTHROMBIN TIME DETERMINATIONS COMPRISING: A PAIR OFELECTRODES, ONE OF SAID ELECTRODES BEING MOVABLE INTO AND OUT OF SAIDSPECIMEN AND THE OTHER OF SAID ELECTRODES BEING STATIONARY IN SAIDSPECIMEN, DRIVE MEANS FOR MOVING THE MOVABLE ELECTRODE INTO AND OUT OFSAID SPECIMEN, FIRST SWITCH MEANS IN SAID CIRCUIT FOR PERMITTING ANELECTRICAL POTENTIAL TO BE APPLIED ACROSS SAID ELECTRODES,SYNCHRONIZATION MEANS SYNCHRONIZED WITH THE OPERATION OF SAID DRIVEMEANS FOR REMOVING THE ELECTRICAL POTENTIAL ACROSS SAID ELECTRODES WHENSAID MOVABLE ELECTRODE IS IMMERSED IN SAID SPECIMEN AND FOR PERMITTINGTHE APPLICATION OF SAID ELECTRICAL POTENTIAL WHEN SAID MOVABLE ELECTRODEIS OUT OF SAID SPECIMEN, SAID SYNCHRONIZATION MEANS INCLUDING SWITCHCLOSING MEANS FOR CLOSING SAID SWITCH UPON LIFTING OF FIBRIN FROM SAIDSPECIMEN BY THE MOVABLE ELECTRODE TO THEREBY PROVIDE A CURRENT PATHBETWEEN SAID ELECTRODES THROUGH THE FIBRIN AND SPECIMEN, AND ELECTRICALMEANS IN RESPONSE TO SAID SWITCH CLOSING MEANS FOR DEACTIVATING THEOPERATION OF THE DRIVE MEANS WHEN THE CURRENT PATH BETWEEN SAIDELECTRODES IS SO PROVIDED, A SECOND SWITCH MEANS FOR ENERGIZING SAIDDRIVE MEANS, MAGNETIC MEANS DRIVEN BY SAID DRIVE MEANS, A MAGNETICALLYEXCITABLE SWITCH ADAPTED TO BE CLOSED UPON EACH TRAVERSAL OF SAIDMAGNETIC MEANS IN CLOSE PROXIMITY THERETO, A COUNTER COUPLED WITH SAIDMAGNETICALLY EXCITABLE SWITCH AND ADAPTED TO REGISTER A DIGITAL AMOUNTUPON EACH CLOSURE OF SAID MAGNETICALLY EXCITABLE SWITCH.